Metabolic bone disorders

Grouped into:

  • Conditions with altered bone mineralisation
  • Conditions with altered bone density but normal mineralisation

Conditions with Altered Bone Mineralisation

  1. Hypercalcaemia
  2. Hypocalcaemia
  3. Rickets
  4. Osteomalacia

Hypercalcaemia

Symptoms:

  • “Bones, groans, stones, and psychic moans”

Causes:

  1. Primary Hyperparathyroidism
  2. Malignancy
  3. Hypocalciuric Hypercalcaemia
  4. Milk Alkali Syndrome
  5. MEN 1 & 2

Primary Hyperparathyroidism:

  • Usually caused by a parathyroid adenoma
Test Results
Blood Calcium high, Phosphate low
PTH levels high
Urine Calcium low/normal
Phosphate high
Radiology Shaggy trabeculae, Pepperpot skull
Subperiosteal osteopenia in fingers
Brown tumours, Chondrocalcinosis

Histology: - Active osteoblasts and osteoclasts - Wide osteoid seams (similar to Paget’s disease)

Malignancy:

  1. Primary ectopic PTH secretion (Small cell lung cancer)
  2. Metastatic disease (stimulates osteoclasts)
  3. Haematologic malignancy (myeloma inhibits osteoblasts, causes bone resorption)

Familial Hypocalciuric Hypercalcaemia:

  • Kidney’s inability to clear calcium leads to serum hypercalcaemia
  • Blood calcium high, Phosphate low or normal

Other Rare Causes:

  • Addison’s disease
  • Milk Alkali Syndrome (Peptic ulcer disease)
  • MEN 1 and 2

Hypocalcaemia

Symptoms:

  • Neuromuscular irritability, depression, cardiac arrhythmia

Causes:

  • Any cause of low PTH or Vitamin D
    • Hypoparathyroidism
    • Pseudohypoparathyroidism
    • Renal osteodystrophy

Hypoparathyroidism:

  • Commonly iatrogenic (post-thyroidectomy)
Test Results
Blood PTH low, Calcium low, Phosphate high
Alkaline Phosphatase normal
Active Vitamin D low
Urine Calcium high or normal
Phosphate low or normal

Pseudohypoparathyroidism:

  • Abnormal PTH dysfunction
  • Albright Hereditary Osteodystrophy (BORESS)
Test Results
Blood PTH high, Calcium low, Alkaline Phosphatase normal
Urine Low calcium and phosphate

Renal Osteodystrophy:

  • Caused by chronic renal failure
  • Two types: High turnover and Low turnover

High Turnover Type:

  • Kidney failure results in hypocalcaemia and high phosphate
  • Causes secondary hyperparathyroidism
  • High osteoblast and osteoclast activity
Test Results
Blood PTH high, Alkaline Phosphatase high, Phosphate high, Calcium low
Clinical Problems Diffuse bone pain, Growth retardation, SUFE
Radiology Ectopic calcium deposition, Rugger Jersey Spine, Osteopenia, Subperiosteal erosion, Looser’s zones

Low Turnover Type:

  • Due to inadequate renal secretion of aluminium, which is toxic to osteoblasts
  • Causes poor bone mineralisation (osteomalacia)

Osteomalacia / Rickets

  • Inadequate mineralisation of the matrix of bone (osteoid) or cartilage (Rickets)
  • Rickets occurs in children, Osteomalacia in adults

Rickets:

  • Most common form: Hypophosphataemic Vitamin D resistant Rickets (X-linked dominant)
Test Results
Blood Alkaline Phosphatase high, Vitamin D normal, Calcium normal, Phosphate low
Urine Phosphate high, Calcium normal
Management Treat with phosphate and high-dose Vitamin D

Other Types: - Vitamin D deficiency or hereditary Vitamin D dependent Rickets

Clinical Features: 1. Short stature 2. Bowing of legs 3. Frontal bossing 4. Dental disease 5. Rachitic Rosary 6. Harrison’s sulcus

X-Ray Features: 1. Haziness of the physis 2. Widened physis 3. Metaphyseal cupping and flaring 4. Coxa vara 5. Bowing of diaphyses 6. Looser’s zones

Osteomalacia:

  • Causes generalised bone pain and stress fractures in adults
  • Most common cause: Vitamin D deficiency
X-Ray Features Histology
Looser’s Zones, Pseudofractures, Biconcave vertebrae Widened osteoid seams
Pelvic deformity, Thin cortices, Bowed tibiae/femora Positive tetracycline labels

Conditions of Altered BMD but Normal Mineralisation:

  1. Osteoporosis
  2. Osteopetrosis
  3. Paget’s Disease

These conditions involve the organic matrix (collagen) but do not affect mineralisation.

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